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Wahl, A. ; Kasela, S.* ; Monotoro, E.C.* ; van Iterson, M.* ; Štambuk, J.* ; Sharma, S. ; van den Akker, E.* ; Klaric, L.* ; Benedetti, E. ; Razdorov, G.* ; Trbojević-Akmačić, I.* ; Vučković, F.* ; Ugrina, I.* ; Beekman, M.* ; Deelen, J.* ; van Heemst, D.* ; Heijmans, B.T.* ; Benedetti, E. ; Wuhrer, M.* ; Plomp, R.* ; Keser, T.* ; Šimurina, M.* ; Pavić, T.* ; Gudelj, I.* ; Krištić, J.* ; Grallert, H. ; Kunze, S. ; Peters, A. ; Bell, J.T.* ; Spector, T.D.* ; Milani, L.* ; Eline Slagboom, P.* ; Lauc, G.* ; Gieger, C.

IgG glycosylation and DNA methylation are interconnected with smoking.

Biochim. Biophys. Acta-Gen. Subj. 1862, 637-648 (2018)
Postprint DOI PMC
Open Access Green
Background: Glycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function of immunoglobulin G (IgG) alters between pro- and anti-inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex and dynamic. Methods: With the use of two different analytical methods for assessing IgG glycosylation, we aim to elucidate the link between DNA methylation and glycosylation of IgG by means of epigenome-wide association studies. In total, 3000 individuals from 4 cohorts were analyzed. Results: The overlap of the results from the two glycan measurement panels yielded DNA methylation of 7 CpG-sites on 5 genomic locations to be associated with IgG glycosylation: cg25189904 (chr.1, GNG12); cg05951221, cg21566642 and cg01940273 (chr.2, ALPPL2); cg05575921 (chr.5, AHRR); cg06126421 (6p21.33); and cg03636183 (chr.19, F2RL3). Mediation analyses with respect to smoking revealed that the effect of smoking on IgG glycosylation may be at least partially mediated via DNA methylation levels at these 7 CpG-sites. Conclusion: Our results suggest the presence of an indirect link between DNA methylation and IgG glycosylation that may in part capture environmental exposures. General significance: An epigenome-wide analysis conducted in four population-based cohorts revealed an association between DNA methylation and IgG glycosylation patterns. Presumably, DNA methylation mediates the effect of smoking on IgG glycosylation.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Dna Methylation ; Igg Glycosylation ; Smoking ; Ewas ; Mediation; Hydrocarbon Receptor Repressor; Epigenome-wide Association; Immunoglobulin-g; Lung-cancer; Alkaline-phosphatase; F2rl3 Methylation; N-glycosylation; Epigenetic Regulation; Ovarian-cancer; Human Placenta
ISSN (print) / ISBN 0304-4165
e-ISSN 1872-8006
Journal Biochimica et Biophysica Acta - General Subjects
Quellenangaben Volume: 1862, Issue: 3, Pages: 637-648 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Computational Biology (ICB)